Skin cancer affects 60% of Australians. Nicotinamide (vitamin B3) prevents many of sunlight’s damaging effects and reduces premalignant keratoses by 35% compared to placebo in sun-damaged individuals. We now need to test whether nicotinamide can prevent skin cancer. Skin cancer patients will receive nicotinamide or placebo for 12 months and new cancers will be counted in each group. Nicotinamide is safe, widely available and an exciting opportunity for cost-effective skin cancer prevention.
Cancers of the skin are the most common tumours in humans, and their diagnosis and treatment impose the largest costs on Australia’s cancer budget. While much has been learned about the roles of sunlight and skin type as risk factors for skin cancer, relatively little is known about the genes conferring risk. This study will compare the genetic profiles of over 6000 patients with skin cancer to 3000 people without skin cancer to pinpoint the genes responsible for skin cancer.
The Role Of Cholesterol In Patched/hedgehog Signalling During Mammalian Development.
Funder
National Health and Medical Research Council
Funding Amount
$198,660.00
Summary
Fluctuations in levels of cholesterol during development of the mammalian embryo have been shown to have catastrophic affects leading to gross deformities particularly in terms of brain and facial development. The requirement of the developing embryo for cholesterol has been linked to the patched-hedgehog signalling pathway which we have previously shown to be central to mammalian development as well as tumour formation. In particular, the patched protein which is responsible for regulating sign ....Fluctuations in levels of cholesterol during development of the mammalian embryo have been shown to have catastrophic affects leading to gross deformities particularly in terms of brain and facial development. The requirement of the developing embryo for cholesterol has been linked to the patched-hedgehog signalling pathway which we have previously shown to be central to mammalian development as well as tumour formation. In particular, the patched protein which is responsible for regulating signalling through this complex cascade of protein interactions has a domain similar to that which in other proteins has been shown to detect and respond to intracellular levels of cholesterol. The patched protein binds to hedgehog at the surface of the cell and mediates the transduction of the the hedgehog signal into the cell. By analogy to the role of sterol sensing domains in other proteins, we hypothesise that this domain in patched detects fluctuations in intracellular cholesterol levels which in turn alter trafficking of patched to the cell surface where it can participate in the hedgehog receptor complex. This hypothesis is supported by our preliminary data which suggests that patched is normally localised both at the cell surface and intracellularly. We are proposing a series of experiments to test our hypothesis, most of which deal with determing the localisation of patched in a cell culure system exposed to agents aimed at varying the intracellular levels of cholesterol. Subcellular localisation of patched will be analysed by immunofluorescence, electron microscopy and immunoblotting analysis. We will also test the ability of patched to aggregate at the cell surface with other molecules important in receiving and sending the hedgehog signal. The experiments in this proposal are likely to give the first clues as to the function of the sterol sensing domain in patched and its role in mediating the vital link between cholesterol and embryonic development.Read moreRead less
Kidskin: An Intervention To Reduce Sun Exposure In Children
Funder
National Health and Medical Research Council
Funding Amount
$307,775.00
Summary
Melanoma is an important public health problem in Australia. Almost all melanoma is caused by exposure to sunlight, and childhood exposure appears to be particularly important. Thus, if we can reduce childhood exposure, we should ultimately be able to reduce the incidence of melanoma. Despite nation-wide campaigns such as SunSmart, children in Australia still get too much sun exposure. The school offers an ideal opportunity for implementing sun-safety campaigns in children. In 1995, we began the ....Melanoma is an important public health problem in Australia. Almost all melanoma is caused by exposure to sunlight, and childhood exposure appears to be particularly important. Thus, if we can reduce childhood exposure, we should ultimately be able to reduce the incidence of melanoma. Despite nation-wide campaigns such as SunSmart, children in Australia still get too much sun exposure. The school offers an ideal opportunity for implementing sun-safety campaigns in children. In 1995, we began the Kidskin study, which aims to develop, implement and test a school-based program to reduce sun exposure. Preliminary data from the study show that we successfully reduced exposure. However, we are not certain that we have reduced their risk of melanoma. To see if we have reduced the risk of melanoma, we are counting the children's moles. Moles are strongly related to melanoma, and are our best way of measuring actual risk of melanoma. If we are successful, it will be the first time anyone has shown that reducing exposure to sunlight during childhood will lead to a reduction in the incidence of melanoma in later life.Read moreRead less
Fighting Epidermal Skin Cancers By Targeting Epidermal Clones That Accumulate Mutations
Funder
National Health and Medical Research Council
Funding Amount
$1,149,373.00
Summary
Common skin cancers such as basal and squamous cell carcinomas (BCC and SCC) are by far the most frequent cancer worldwide and require over a million interventions per year in Australia. This project will identify the skin cells that are most susceptible to give rise to cancer if excessively exposed to the sun and explores ways to prevent cancer formation. This will inform on new strategies to prevent new skin cancer development.
Case-control Study Of Reasons For Presentation Of Nonmelanocytic Skin Cancers At An Advanced Stage.
Funder
National Health and Medical Research Council
Funding Amount
$250,614.00
Summary
There are about four times as many skin cancers treated in Australia each year as all other cancers combined and the vast majority of these are the nonmelanocytic skin cancers (NMSC). While most of these cancers are easily treatable, a proportion of these cancers are not given potentially effective treatment until the cancer has reached an advanced stage. Preliminary results from our pilot studies indicate that at least 50% of patients with NMSC who are treated with radiotherapy and 92% of NMSC ....There are about four times as many skin cancers treated in Australia each year as all other cancers combined and the vast majority of these are the nonmelanocytic skin cancers (NMSC). While most of these cancers are easily treatable, a proportion of these cancers are not given potentially effective treatment until the cancer has reached an advanced stage. Preliminary results from our pilot studies indicate that at least 50% of patients with NMSC who are treated with radiotherapy and 92% of NMSC patients treated with a graft or flap surgical procedure by the dermatologists in Newcastle are so treated because of the extent of disease at the primary site. These advanced stage cancers make an important contribution to the 70,000 admissions to hospital for the treatment of NMSC each year in Australia. The total direct health services cost of treatment of these skin cancers was estimated to be $232,000,000 in 1993-94, which was more than for any other type of cancer. Some 379 people died from nonmelanocytic skin cancer in Australia in 1993 and these were all potentially preventable deaths. The study aims are therefore to: 1. Measure the contributions of delay in seeking treatment and inadequate inital treatment to the need for treatment of skin cancer at an advanced stage. 2. Ascertain the factors that are associated with delay in seeking treatment for skin cancer until it has reached an advanced stage. This study will be the first substantial and population-based study of advanced skin cancer and the factors that underlie it. It will give the first empirical guidance to the design of initiatives to prevent the development of advanced skin cancer, a major area of cost to Australian health services. The study will increase understanding of why some skin cancers are not treated definitively until they reach an advanced stage and guide the development of interventions to reduce the frequency of patients who present with advanced stage skin cancer.Read moreRead less
Clinical Trial Of DZ13 DNAzyme Targeting C-Jun In Subjects With Basal Cell Carcinoma - DISCovery (Oligonucleotide Inhibition Of Skin Cancer) Study
Funder
National Health and Medical Research Council
Funding Amount
$74,365.00
Summary
Basal cell carcinoma (BCC) is the commonest skin cancer in Australia that is highly invasive. Surgical removal is its main treatment option but causes scarring and is impractical when there are multiple cancers. C-Jun, a molecule promoting cell growth is present in abnormally large amount in BCC compared to normal cells. Dz13 targets and destroys these molecules, killing cancer cells when injected into the tumour. Dz13 may hence become a more effective and aesthetic alternative of treating BCC.